Search

Purpose Postoperative hypoparathyroidism remains the most often complication in thyroid surgery. Near-infrared autofluorescence (NIR-AF) is a modality to identify parathyroid glands (PG) in vivo with high accuracy, but its use in daily routine surgery is unclear so far. In this randomized controlled trial, we evaluate the ability of NIR-AF to prevent postoperative hypoparathyroidism following total thyroidectomy. Methods Patients undergoing total thyroidectomy were allocated in two groups with the use of NIR-AF in the intervention group or according to standard practice in the control group. The aim was to identify the PGs in an early most stage of the operation to prevent their devascularization or removal. Parathyroid hormone was measured pre- and postoperatively and on postoperative day (POD) 1. Serum calcium was measured on POD 1 and 2. Possible symptoms and calcium/calcitriol supplement were recorded. Results A total of 60 patients were randomized, of whom 30 underwent NIR-AF-based PG identification. Hypoparathyroidism at skin closure occurred in 7 out of 30 patients using NIR-AF, respectively, in 14 out of 30 patients in the control group (p=0.058). There was no significant difference in serum calcium and parathyroid hormone levels between both groups. Likewise, NIR-AF could not detect PGs at a higher rate. Conclusion The use of NIR-AF may help surgeons identify and preserve PGs but did not significantly reduce the incidence of postoperative hypoparathyroidism in this trial. Larger case series have to clarify whether there is a benefit in routine thyroidectomy. Trial registration number DRKS00009242 (German Clinical Trial Register). Registration date: 03.09.2015

Chief cells are the predominant cells in parathyroid glands of healthy adults; however, parathyroid oxyphil cells, whose function is unknown, increase dramatically in patients with secondary hyperparathyroidism (SHPT). Calcitriol and calcimimetics are the most powerful treatments for SHPT, while the mechanisms leading to calcitriol or calcimimetic resistance in oxyphil cell-predominant SHPT are unknown. Here we used transcriptomic and proteomic techniques to characterize oxyphil cells by comparing the differences between chief and oxyphil cell nodules of parathyroid glands in uremic patients. Compared to chief cell nodules, the most marked expression increases in oxyphil cell nodules were for mitochondrion-associated proteins. The mitochondria number and mitochondrial DNA content were also significantly increased in oxyphil cell nodules. Moreover, oxyphil cell nodules expressed parathyroid-specific factors, and exhibited lower levels of proliferation-related proteins but higher synthesis and secretion level of parathyroid hormone (PTH). The protein expression of SHPT-regulating factors, including vitamin-D receptor, calcium-sensing receptor and Klotho, were significantly downregulated in oxyphil cell nodules. Therefore, oxyphil cells characterized by enrich mitochondria in uremic patients showed higher synthesis and secretion of PTH but lower expression of SHPT regulators than chief cells, which may contribute to the pathophysiology of SHPT and the treatment resistance to calcitriol and calcimimetics.

Purpose: Accidental injury to the parathyroid glands (PTGs) is common during thyroid and parathyroid surgery. To overcome the limitation of naked eye in identifying the PTGs, intraoperative autofluorescence imaging has been embraced by an increasing number of surgeons. The aim of our study was to describe the technique and assess its utility in clinical practice. Methods: Near-infrared (NIR) autofluorescence imaging was carried out during open parathyroid and thyroid surgery in 25 patients (NIR group), while other 26 patients underwent traditional PTG detection based on naked eye alone (NO-NIR group). Primary variables assessed for correlation between traditional approach and autofluorescence were number of PTGs identified and incidence of postoperative hypoparathyroidism (hypoPT). Results: 81.9% of PTGs were detected by means of fluorescence imaging and 74.5% with visual inspection alone, with an average of 2.72 PTGs visualized per patient using NIR imaging versus approximately 2.4 per patient using naked eye (p = 0.38). Considering only the more complex total thyroidectomies (TTs), the difference was almost statistically significant (p = 0.06). Although not statistically significant, the observed postoperative hypoPT rate was lower in the NIR group. Conclusion: Despite the limitations and technical aspects still to be investigated, fluorescence seems to reduce this complication rate by improving the intraoperative detection of the PTGs.

There are scant data in the literature regarding whether parathyroid autofluorescence (AF) signal patterns vary based on the etiology of hyperparathyroidism. The aim of this study was to compare AF signals of parathyroid glands across different etiologies of hyperparathyroidism.As a prospective institutional review board-approved study between 2016 and 2019, AF intensities and heterogeneity indexes (HIs) of parathyroid glands in patients who underwent parathyroidectomy using AF were calculated and compared using Chi-square, Kruskal Wallis, Mann Whitney U, and logistic regression tests.Of the total of 183 patients, 127 patients had sporadic classic primary hyperparathyroidism, 30 patients had sporadic normohormonal primary hyperparathyroidism, 10 patients had sporadic normocalcemic primary hyperparathyroidism, 12 patients had tertiary hyperparathyroidism, and 4 patients had familial primary hyperparathyroidism related to multiple endocrine neoplasia (MEN) 2A. There were no statistical differences in AF signals of abnormal parathyroid glands in classic, normohormonal or normocalcemic sporadic hyperparathyroidism. Parathyroid glands in patients with tertiary hyperparathyroidism were similar in intensity, but more homogenous compared to those in sporadic primary hyperparathyroidism.The pattern of AF exhibited by abnormal parathyroid glands was similar across different spectrums of primary hyperparathyroidism, in accordance with observations in the literature. However, parathyroid glands in tertiary hyperparathyroidism were more homogeneous, despite exhibiting a similar intensity of AF compared to those in sporadic primary hyperparathyroidism. These differences should be kept in mind when using the AF pattern as an adjunct to visual assessment in parathyroid exploration.

We compared the reliability of indocyanine green (ICG) angiography and intraoperative PTH levels for predicting early post-thyroidectomy hypocalcemia. Prospective study of 94 patients (71% women, mean age 53.7 years) undergoing total thyroidectomy. An ICG score of 2 (white) indicated a well-vascularized gland. PTH preoperative levels—PTH postresection levels divided by preoperative PTH × 100 was used to determine the PTH decline percentage. A decrease of at least 62.5% or

To evaluate the diagnostic accuracy of near-infrared autofluorescence-based identification in the identification of parathyroid glands during thyroidectomy or parathyroidectomy. The clinical studies were retrieved from PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, SCOPUS, and Google Scholar. The study protocol was registered on Open Science Framework ( https://osf.io/um8rj/ ). The search period ranged from the date of each database’s inception to May 2021. Cohort studies dealing with patients of whom parathyroid glands were detected by near-infrared autofluorescence and confirmed clinically or pathologically during thyroidectomy or parathyroidectomy were included. Editorials, letters, “how-I-do-it” descriptions, other site head and neck tumors, and articles with lack of diagnostic identification data were excluded. True positive, true negative, false positive, and false negative were extracted. The QUDAS ver. 2 was used to evaluate the methodological quality. Seventeen studies with 1198 participants were evaluated in this analysis. Near-infrared autofluorescence-based identification of parathyroid glands showed a diagnostic odds ratio of 228.8759 (95% confidence interval, 134.1099; 390.6063). The area under the summary receiver operating characteristic curve was 0.967. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.9693 (0.9491; 0.9816), 0.9248 (0.8885; 0.9499), 0.9517 (0.8981; 0.9778), and 0.9488 (0.9167; 0.9689), respectively. Subgroup analyses were performed to compare two autofluorescence detection methods, because there was high heterogeneity in the outcomes. The diagnostic accuracy was higher in probe-based detection than in image-based detection. Near-infrared autofluorescence-based identification is valuable for identifying the parathyroid glands of patients during thyroidectomy or parathyroidectomy.

The role of oxyphil cells (OxC) in primary hyperparathyroidism (PHPT) still remains controversial. Historically, they were believed to be involuted cells. However, they could play an important role in hormone secretion. The clinical behavior of OxC-rich adenomas and preoperative PHPT localization tests have been widely studied. The aim of this study is to analyze the implications of OxC in PHTP. A retrospective cohort study of patients undergoing parathyroidectomy for PHPT was conducted. Additionally, we included normal glands removed in the context of PHPT or inadvertently during a thyroidectomy. All glands were reviewed independently by three researchers, performing a semi-quantitative analysis of the percentage of OxC. Groups with 75% OxC were compared. In the period 2010–2017, 238 patients and 261 removed glands were included (8.8% OxCA > 75%). There were no differences in symptomatology and levels of preoperative calcium, parathormone, or 25-OH vitamin. Patients with OxCA > 75% had worse preoperative glomerular filtration rate (81.2 vs. 69.7 mL/min/1.73 m2; p = 0.043). They also had a trend towards larger size and weight (17 vs. 20 mm, p = 0.135 and 562 vs. 875 mg, p = 0.495), while ultrasound was found to have better accuracy (48.3% vs. 73.7%; p = 0.035). There were no normal glands with a content of OxC > 75%. Our study suggests that phosphocalcic metabolism is not influenced by the presence of a high content of OxC in the parathyroid glands. A high content of OxC seems to be exclusive to pathologic glands and could be related to the deterioration of renal function in patients with PHPT.

IntroductionNuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration.MethodsOver a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT.ConclusionThese guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.

Recently, there are many new surgical methods of endoscopic thyroidectomy, which have advantages in cosmetic results while do not increase the complication rates. This study was conducted to evaluate and compare both intra- and post-operative results and quality of life between TOETVA and endoscopic thyroidectomy axillo-breast approach (ETABA). A non-randomized, patient preference clinical trial was performed in Otorhinolaryngology, Head and Neck surgery department, HRH Princess Maha Chakri Sirindhorn Medical center. Patients who decided to go for endoscopic thyroidectomy were allocated into two groups. Demographics data, operative time, intra-operative blood loss, post-operative pain score, length of hospital stay, complications were collected. Overall satisfaction was evaluated by visual analogue scale and quality of life was evaluated by SF-36 questionnaires. 22 patients were totally included and equally allocated in 2 groups (11 patients per group). All of the operations were lobectomy. There was no significant difference in demographic data. The results showed that pain score at 3 days post-operation and average pain score were significantly higher in TOETVA group. Average pain score was 3.67 ± 1.11 in ETABA group and 5.15 ± 1.35 in TOETVA (p = 0.011); however, the operative time, intra-operative blood loss, length of hospital stay, complications and overall satisfaction were not significantly different. Different change in the quality of life was not detected in both groups. Transoral endoscopic thyroidectomy vestibular approach and ETABA both have comparable results and do not worsen the quality of life.

Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion. The PTH–calcium setpoint and maximum and minimum PTH secretion were determined using an ‘in vivo setpoint analyses.’ The PTH–calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry. Etelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups. Etelcalcetide decreased the PTH–calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.

Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown. This study aimed to determine if etelcalcetide suppresses parathyroid hormone secretion by human parathyroid cells in vitro. We prepared primary cell cultures from human parathyroid tissue and determined calcium-sensing receptor expression levels by immunohistochemistry. Pathyroid tumors were removed from fourteen patients with primary hyperparathyrodism. Parathyroid tissue was dispersed with collagenase, resuspended in culture medium, incubated for 2 h with etelcalcetide and Ca2+, and the medium was then collected. Final etelcalcetide concentrations in the medium were 0.005–50 µmol/L. Levels of human parathyroid hormone in the medium were determined by enzyme-linked immunosorbent assay. In eight of the fourteen parathyroid cell cultures, extracellular Ca2+ reduced parathyroid hormone levels. In four of the eight parathyroid cell cultures which responded extracellular Ca2+, etelcalcetide reduced hormone secretion with the 50% effective concentrations of 0.57, 20.8, 0.42, and 0.57 µmol/L. Expression levels of the calcium-sensing receptor were significantly lower in primary hyperparathyroidism patient-derived parathyroid tissues compared with controls. This is the first report that etelcalcetide directly reduced parathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism. To verify this conclusion, further studies are needed using secondary hyperparathyroidism patient-derived parathyroid cells.

The objective of this study was to retrospectively evaluate preoperative imaging modalities for localization of parathyroid adenomas with a view to enable minimally invasive parathyroidectomy and in particular, to consider the contribution of 18F-fluorocholine-PET/CT. 104 patients with primary hyperparathyroidism, who underwent parathyroid surgery in a single centre during a 6-year period were included. Of these, 103 underwent ultrasound, 97 99mTc-Pertechnetate/SestaMIBI-SPECT, 20 MRI and 30 18F-fluorocholine-PET/CT. Based on surgical findings, sensitivities and specificities for correct lateralisation in orthotopic locations were: for ultrasound 0.75 (0.65–0.83) and 0.89 (0.81–0.94), for 99mTc-MIBI-SPECT 0.57 (0.46–0.67) and 0.97 (0.91–0.99), for MRI 0.60 (0.36–0.81) and 0.83 (0.59–0.96) and for 18F-fluorocholine-PET/CT 0.90 (0.73–0.98) and 0.90 (0.73–0.98). Correctly lateralized adenomas were significantly larger than those not found with ultrasound (p = 0.03) and SPECT (p = 0.002). Pre-operative PTH-levels were higher in single adenomas detected by scintigraphy than in those not (p = 0.02). 64 patients could be treated with a minimally invasive procedure. Cure after parathyroidectomy was obtained in 94% of patients. 18F-Fluorocholine-PET/CT could be shown to be a highly accurate modality to localize parathyroid adenomas preoperatively, obviating the need for total exploration in the majority of patients in whom ultrasound and scintigraphic results are discordant or both negative.

The aim of this study was to elucidate the causes of false-negative cases of technetium-99 m methoxyisobutylisonitrile scintigraphy (MIBI) for hyperparathyroidism. Consecutive MIBI examinations performed in 154 patients between April 2011 and March 2017 were retrospectively reviewed. Sensitivities of MIBI, CT and US were calculated. The effects of serum calcium, phosphorus, PTH, weight of parathyroid lesions, use of NSAIDs and Ca-channel blocker (CCB), presence of cyst in parathyroid lesions, and a number of lesions observed by MIBI were investigated. Seventy-nine patients (21 men and 58 women), ranging from 18 to 88 years of age (mean ± SD: 57.6 ± 15.3 years), who underwent parathyroidectomy, were included. MIBI and preoperative US were performed in the 79 patients and single-phase parenchymal contrast-enhanced CT (CE-CT) was performed in 55 patients. A total of 120 parathyroid proliferative nodules were detected by MIBI and US, and 92 lesions were detected by CE-CT. In the lesion base, MIBI detected 82 out of the 120 lesions (sensitivity = 68.3%), US detected 103 out of the 120 lesions (sensitivity = 85.8%), CE-CT detected 63 out of the 92 lesions (sensitivity = 68.5%), and MIBI plus CE-CT detected 72 of the 92 lesions (sensitivity = 78.3%). A significant difference in the sensitivity was found between US and MIBI (P

This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor-binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.

PURPOSE: The purpose of this study is twofold: 1) to determine the feasibility of optical coherence tomography (OCT) to differentiate normal and diseased tissue of the neck region intra-operatively, and 2) to evaluate how accurately a cohort of test subjects can identify various tissue types when shown a sample set of OCT images. METHODS: In this in vivo, prospective, single institutional study, an OCT imaging system (Niris, Imalux, Cleveland, OH) was used to image parathyroid, thyroid, lymph node, and fat tissue in 76 patients during neck surgery. Biopsies were performed for comparison of OCT images to histology in select cases (n=20). Finally, a group of either surgeons or scientists familiar with OCT (n=17) were shown a sample of OCT images and asked to identify the tissue. RESULTS: A total of 437 OCT images were analyzed and characteristic features of each tissue type were identified. OCT demonstrated distinct differences in structural architecture and signal intensity that differentiation between thyroid and parathyroid tissues, lymph nodes, and fat. OCT images were also compared with histology with good correlation. There was no difference in correctly identifying OCT imaged tissue type between surgeons and scientists. CONCLUSION: This study is the first in vivo OCT imaging study to evaluate both normal and diseased tissues that may be encountered during neck surgery. OCT has the otential to become a valuable intra-operative tool to differentiate diseased and normal thyroid tissue. intraoperatively to obtain an “optical biopsy” in real time without fixation, staining, or tissue resection.

A reticulin staining pattern (RSP) can be used for the differential diagnosis of endocrine gland lesions, as in the adrenal and hypophysis glands. We aimed to use RSP for the differential diagnosis of parathyroid gland lesions. In this study, we evaluated 97 parathyroid lesions in 85 patients, as well as 29 normal parathyroid glands. All sections were stained with a silver impregnation-based kit for the reticulin stain. The RSPs were classified as short thick fiber-, anastomosing- and nodular/alveolar-pattern. The dominant pattern was accepted as being greater than 50% in each section. Short thick fibers and anastomosing and nodular RSPs were seen in adenomas, but there was no alveolar pattern. Although nodular/alveolar patterns were seen in focal areas in hyperplasia, they never became the dominant pattern. Nodular dominant RSPs were seen in adenomas; however, nodular RSPs were not seen in hyperplasia in a dominant pattern (p = 0.049). While short thick fibers were not seen in normal glands, they could be seen in adenomas (p

BACKGROUND: Primary hyperparathyroidism (PHPT) in children and adolescents is uncommon. Data-driven guidelines for management in pediatric patients are limited. METHODS: We performed a retrospective cohort analysis of all patients (1997-2017) with PHPT ≤21 years of age who underwent parathyroidectomy at three institutions. Clinical and demographic variables were analyzed. Primary operative outcome was cure (normocalcemia >6 months after surgery); secondary outcome was operative success (intraoperative parathyroid hormone (IOPTH) decrease of ≥50%). RESULTS: We identified 86 patients with a median age of 17 years (IQR:14,19); 64% (n=55) were female. The mean preoperative serum calcium was 11.7 mg/dL, median parathyroid hormone (PTH) was 110 pg/mL, and median urine calcium was 4.1 mg/kg/24 hours. Preoperatively, sestamibi scan localized in 41/71 patients (58%); neck ultrasound localized in 19/44 (43%). The most common pathology at surgery was a single eutopic parathyroid adenoma in 71% (n=61). A high incidence of ectopic adenomas (25%, n=22) was observed, most commonly intrathymic (n=13), followed by tracheoesophageal groove (n=5), carotid sheath (n=2) and intrathyroidal (n=2). Of 56 patients with retrievable data >6 months postoperatively, cure was achieved in 55 of 56 patients (98%). One patient who presented to us with parathyromatosis requiring subsequent reoperation. CONCLUSION: In this multi-institutional series of PHPT in children and adolescents, the majority were sporadic PHPT and were due to a single adenoma. We observed a high incidence of ectopic parathyroid adenomas, most commonly intrathymic. Given the high risk for ectopic adenoma in pediatric patients, parathyroid surgery in children and adolescents should be performed by experienced surgeons.

Purpose: Recently, it has been demonstrated that Raman spectroscopy is able to differentiate between healthy parathyroid tissues and parathyroid adenoma based on the basis of a specific molecular fingerprint. However, to our knowledge, no previous studies have been performed to evaluate the metabolic profile of parathyroid adenoma. Therefore, we designed a proof of concept study aimed to investigate the glucose/fatty acid metabolisms, in addition to the mitochondrial changes, in solitary parathyroid adenoma and in healthy parathyroid glands. Methods: Nine females with primary hyperparathyroidism due to a solitary parathyroid adenoma and formal surgical indication for parathyroidectomy have been enrolled. At the time of surgery, the removed specimens were immediately submitted unfixed and a tissue slice of about 0.5 cm in diameter was obtained from the nodular lesion. The expression of selected metabolic enzymes and proteins has been evaluated by western blot analysis, using human parathyroid whole tissue lysates as control. Results: Data obtained highlighted an increase, compared with the healthy group, of: (i) the glucose uptake by the GLUT-1 receptor and its phosphorylation by hexokinase II (HXKII); (ii) the expression of 3-phosphoglycerate dehydrogenase (3-PGDH) and glucose-6-phosphate dehydrogenase (G6PD); (iii) lipids biosynthesis; and (iv) cytochrome c expression. Conclusions: Our findings highlight for the first time the parathyroid adenoma metabolic hallmarks that could represent potential molecular targets usable for the development of new pharmacological treatments, allowing to reduce surgical parathyroidectomy.

PURPOSE: Parathyroid cancer is a rare tumor associated with poor prognosis particularly when disseminated. While chemotherapy and/or radiotherapy are of no clinical value in disseminated disease, immunotherapy should be considered. SUBJECT AND RESULTS: A patient with CDC73-associated metastatic parathyroid carcinoma was treated with combined anti-hPTH immunotherapy and surgery. CONCLUSIONS: Following five courses of anti-hPTH immunotherapy and subsequent surgery, a 12-year long remission of disseminated parathyroid cancer is reported. This case further supports the ever-expanding spectrum of cancers that may benefit from immunotherapy.

We investigated outcomes in a cohort of patients with a biochemical diagnosis of primary hyperparathyroidism (pHPT) undergoing surgery for asymptomatic disease or target organ damage, where a focussed or four-gland operation was undertaken and the histopathology only reported a “large normal” parathyroid gland (LNP). Patients subjected to a parathyroidectomy for pHPT between 2012 and 2018 with a pathology of LNP were included. Patients with fat depletion or additional histological features of adenoma or hyperplasia in any of the resected glands were excluded. A control group was formed from 50 consecutive patients with the histological finding of adenoma or hyperplasia during the same study period. The primary outcome was biochemical normalisation of pHPT at 1–2 weeks and after 6 months post-operatively. Forty-eight LNP patients (2% of all parathyroidectomies) were included in the study group with 50 matched controls. LNP patients had a lower biochemical cure rate (81% vs. 98% P

Background Forearm autotransplantation after parathyroidectomy has turned into the standard method for secondary hyperparathyroidism (SHPT) treatment in chronic kidney disease patients. Our study aimed to explore the effects of three methods including muscle, subcutaneous and muscle + subcutaneous transplant methods on SHPT. Methods Seventy five SHPT patients were enrolled and assigned into the muscle + subcutaneous (M + S) (n = 26), muscle (M) (n = 35), and subcutaneous (S) (n = 14) groups. The operation efficacy evaluation included preoperative and postoperative biological characteristics such as parathyroid hormone (PTH), serum phosphorus, serum calcium and alkaline phosphatase (ALP). The data were recorded from pre-operation time point to 1, 2, 3, 6, 12, 18, 24 month (mo) postoperation periods. After operation, short-form health survey (SF-36) scores was made for life quality identification at 1, 2, 3, 6, 12, 24 time points. Symptoms about SHPT including bone pain, fracture, pruritus, and coronary artery calcification were followed-up based on the scale. Results Compared with the preoperative record, all the M + S, M, and S groups showed postoperative decreased levels of PTH, serum phosphorus, serum calcium, calcium-phosphorus. In M + S group, the PTH and serum calcium level kept more steady compared with the M and S groups during a 24 mo duration observation. After this, a SF-36 score scale which represents the life quality show M + S group got more scores at 3, 6, 12, 18 and 24 mo points. At last, the incidence of SHPT associated symptoms including Bone pain, Fracture, Pruritus, and Coronary artery calcification in M + S group were decreased compared with M and S groups at 1, 3, 6, 12 and 24 mo post-operation time points. Conclusion M + S seems to be an efficient method for medical treatment of SHPT patients in the control of PTH and serum calcium. This mixed transplant strategy improves the biochemical characterizes compared with M and S groups in SHPT patients. Furthermore, the M + S method make beneficial on clinical outcomes and life quality of patients.

Background Double adenomas (DA) represents a distinct clinical entity of primary hyperparathyroidism (PHPT). DA may follow various embryologic distribution patterns and could be supernumerary and/or ectopic. Case presentation We describe the first case of PHPT which comes as a result of double ipsilateral adenoma, of which one was both ectopic and supernumerary. A 45 year-old Greek male patient with diagnosed PHPT due to a single lower right parathyroid adenoma was admitted to our department for surgical treatment. The preoperative tests (neck US, Sestamibi scan) were conclusive for single gland disease. The patient underwent focused parathyroidectomy. The frozen section revealed a parathyroid adenoma with a slight possibility for parathyroid carcinoma. Ten minutes after the excision, intact PTH (iPTH) dropped >50% related to preoperative values and was within normal range. Right hemithyroidectomy with additional ipsilateral central neck dissection was performed, because of the possibility for parathyroid carcinoma. The final pathology report showed that the first excised tissue proved to be a parathyroid adenoma, while a second subcapsular one and a normal right upper parathyroid gland were also found. Conclusions Preoperative localization of DA using routine imaging tests and the utility of intraoperative parathyroid hormone assay are still unreliable in detecting multiple adenomas. Furthermore, a slight possibility of a second and simultaneously supernumerary and ectopic adenoma maybe present. Therefore, it would be advisable to establish the use of more advanced imaging tests (such as 4D-CT, 4D-MRI) or other diagnostic tools when DA are suspected.

Purpose A fluorescence-based technique for the detection of parathyroid glands (PGs) intraoperatively was previously reported. The technique was based on the phenomenon in which PGs emit autofluorescence when exposed to near-infrared light and we undertook an evaluation to consider the pathological accuracy of the method. Methods The study comprised 17 patients (18 specimens) who underwent thyroid surgery at Kushiro City General Hospital between November 2018 and June 2019. We searched for PGs intraoperatively using a fluorescence spectroscopy system and evaluated the pathological accuracy of the system. We statistically evaluated the clinical factors associated with the accuracy of the system, including age, gender, body mass index, laterality, disease state, renal function, and comorbidity. Results Eighteen specimens were evaluated pathologically, with 13 specimens confirmed as PGs. These were evaluated as "true positive," giving a positive predictive value of 72.2% (13/18). Among the false-negative cases, one specimen was a metastatic lymph node in a patient with papillary thyroid carcinoma. There was a significant difference in the true-positive rates between malignant (25%) and benign (85.7%) disease (P = 0.044). Conclusion We consider that this technique is useful, however, we have to exercise care in malignant cases as the true-positive rate may be low.

The optimal surgical approach of parathyroidectomy for patients with secondary hyperparathyroidism (SHPT) has been controversial. The updated meta-analysis aimed to compare the effectiveness of subtotal parathyroidectomy (SPTX) versus total parathyroidectomy with autotransplantation (TPTX + AT). A thorough systematic search was performed on the databases of PubMed, EMBASE, and Cochrane library to identify eligible studies. Data were extracted and pooled into a meta-analysis. The primary outcomes were the symptomatic improvement, radiological changes, hypocalcemia rate, the requirement for vitamin D analogues, time to recurrence, recurrence, persistence, and reoperation rates of SPTX versus TPTX + AT. A total of 18 studies with 3656 patients (1864 patients in SPTX and 1792 patients in TPTX + AT group) were included, and 15 studies were included in quantitative synthesis. No significant difference was observed in symptomatic improvement (93.3%, 89.0%; P = 0.99), radiological changes (85.4%, 85.3%; P = 0.91), hypocalcemia rate (16.6%, 18.1%; P = 0.29), persistence rate (6.1%, 2.0%; P = 0.16), time to recurrence (mean difference 1.46; P = 0.87), recurrence rate (9.2%, 7.1%; P = 0.76), and reoperation rate (5.3%, 5.8%; P = 0.66) between SPTX and TPTX + AT groups. Longer operative time (150 vs. 120 min), prolonged in-hospital stay (5.0 vs. 4.1 days), lower 1-month serum calcium level, and higher requirement for vitamin D analogues at 12 months were significantly observed in patients who underwent TPTX + AT compared to SPTX. The two surgical approaches were both effective at controlling SHPT in clinical and laboratory terms. However, most of the data shown were not statistically significant. It was acceptable that surgeons chose either SPTX or TPTX + AT for SHPT.

Cervical esophageal cancer (CEC) patients whose larynx function cannot be preserved often undergo chemoradiotherapy, whereas those with residual or recurrent lesions undergo a pharyngo-laryngo-esophagectomy (PLE); however, some need to undergo a pharyngolaryngectomy with total esophagectomy (PLTE) for synchronous or metachronous esophageal cancer. We retrospectively evaluated the relationship between preoperative irradiation (or the extent of esophageal resection) and postoperative endocrine complications in CEC, including hypothyroidism and hypoparathyroidism. The cancers of 35 (5.4%) of 678 esophageal cancer patients with esophagectomy treated in 2000–2017 were CECs. We also analyzed the 17 cases of CEC patients who underwent PLE with thyroid lobectomy—11 with irradiation before PLE and 6 without irradiation. Seven patients underwent a PLTE. Hypothyroidism and hypoparathyroidism occurred in 14 and 12 patients, respectively. The hypothyroidism rate was significantly higher in patients with irradiation versus those without irradiation (100% vs. 50%; p = 0.010), and the hypoparathyroidism rate was significantly higher in the PLTE versus non-PLTE patients (100% vs. 50%; p = 0.026). The mean levothyroxine dosage was 1.60 μg/kg/day in the PLE patients post-irradiation. Irradiation appears to be a risk factor for hypothyroidism after PLE with thyroid lobectomy, while PLTE might have some effect on hypoparathyroidism. Due to vocal function loss, PLE patients may experience symptoms from endocrine complications. Levothyroxine treatment soon after PLE for post-irradiation patients and patients requiring as-needed calcium or vitamin D supplementation based on biochemical hypocalcemia for PLE (especially PLTE), may be effective in preventing symptomatic endocrine complications.

This study evaluates possible changes in weight and the secretory patterns of the thyroid and parathyroid glands irradiated with a 780-nm light-emitting diode (LED) source under conditions allowing their identification in an animal model. The use of near-infrared light sources to detect the parathyroid glands has been a subject of research due to the benefit provided to patients undergoing thyroid and parathyroid surgery. However, few studies have explored possible changes in weight and the secretory patterns of the glands when subjected to light stimulation. Thirty-two male Wistar rats were divided into two groups and subjected to cervical dissection and irradiation of the thyroid-parathyroid region under general anesthesia. The animals in group 1 (irradiated) were exposed to a 780-nm LED light beam for 180 s (dose 1.37 J/cm2), whereas the animals in group 2 (control) were not irradiated. Blood samples were collected pre-exposure, 7 min after exposure, and 30 and 60 days after exposure to measure calcium, parathyroid hormone (PTH), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels in both groups. Weight variations between the evaluation periods were also analyzed. Parametric statistics were used (Student’s t test and ANOVA) after assuming normal distribution of continuous variables with the Shapiro-Wilk test. No significant variation was observed in any of the analyzed parameters pre- and postexposure. A significant increase in the calcium level was observed at 30 days in the irradiated group compared with that in the control group (11.156 ± 1.31 mg/dl vs 10.300 ± 0.30 mg/dl; df = 30 p

Intraoperative verification of parathyroid glands relies on visual identification by the surgeon and, with some time delay, on serum parathormon measurements and frozen section. Fluorescence imaging, however, is an instant on-table method for direct visualization of parathyroid tissue which is known to exhibit increased autofluorescence intensity when exposed to near-infrared light. In this retrospective observational study, we evaluate the clinical use of this method in a series of patients with primary and secondary hyperparathyroidism. A total of 66 adenomatous and hyperplastic parathyroid glands were examined with intraoperative autofluorescence in 39 patients with primary and secondary hyperparathyroidism using a near-infrared system (KARL STORZ GmbH & Co. KG). The specimens were verified by conventional histology. Fifty-seven of 66 histologically proven adenomatous/hyperplastic glands exhibited autofluorescence. The sensitivity of near-infrared autofluorescence was 0.9 in pHPT and 0.83 in sHPT, respectively. The positive predictive value was 0.93 in pHPT and 1.0 in sHPT, respectively. Near-infrared autofluorescence guidance presents an innovative instant surgical imaging tool with sensitivity in detecting adenomatous and hyperplastic parathyroid glands comparable to current intraoperative methods. Due to its elegant and tracer-free design combined with low follow-up costs, this method can be useful for routine use.

Background Practice variations exist amongst parathyroid surgeons depending on their expertise and resources. Our study aims to elucidate the choice of surgical techniques and adjuncts used in parathyroid surgery by surgeons in the Asia-Pacific region. Methods A 25-question online survey was sent to members of five endocrine surgery associations. Questions covered training background, practice environment and preferred techniques in parathyroid surgery. Respondents were divided into three regions: Australia/New Zealand, South/South East Asia and East Asia, and responses were analysed according to region, specialty, case volume and years in practice. Results One hundred ninety-six surgeons returned the questionnaire. Most surgeons (98%) routinely perform preoperative imaging, with 75% preferring dual imaging with 99mTcsestamibi and ultrasound. Ten per cent of surgeons use parathyroid 4DCT as first-line imaging, more commonly in East Asia (p = 0.038). Minimally invasive parathyroidectomy is the favoured technique of choice (97%). Most surgeons reporting robotic or endoscopic approaches are from East Asia. Rapid intraoperative parathyroid hormone is accessible to just under half of the surgeons but less available in Australian/New Zealand (p

Parathyroidectomy is useful for the treatment of secondary hyperparathyroidism (SHPT) caused by chronic renal failure. The following three types of parathyroidectomy can be performed: subtotal parathyroidectomy, total parathyroidectomy and total parathyroidectomy plus autologous transplantation (tPTX+AT). Each of the three types of surgery has advantages and disadvantages. The present study retrospectively analyzed the efficacy of tPTX+AT for the treatment of SHPT over 1 year. Thirty-seven patients who were diagnosed with secondary nephrogenic hyperparathyroidism and treated with tPTX+AT were selected between September 2014 and October 2016 and followed up for 1 year. Their average age was 66.5±46.0 years, and the average time of dialysis was 48.1±8.2 months. The patients' conditions, including the levels of intact parathyroid hormone (iPTH) and bone metabolism, were compared preoperatively and 1 and 7 days and 1, 3, 6 and 12 months after surgery. In addition, the postoperative complications, pathological data, SHPT recurrence and prognosis were examined. The results showed that the postoperative level of ostalgia and cutaneous pruritus significantly decreased in the patients. An inspection of the parathyroid tissues during the operation confirmed the presence of parathyroid gland hyperplasia with no carcinoma detected. Three patients with hoarseness recovered within 1 month, and 1 patient with unilateral recurrent laryngeal nerve injury improved after 6 months of voice training. Compared to the preoperative condition, the postoperative serum iPTH, serum calcium and serum phosphate levels were significantly decreased (P0.001), and these differences remained significant 12 months after surgery. Compared to the preoperative condition, the alkaline phosphatase (ALP) concentration was decreased on postoperative day 1 (P0.05), but no differences were observed on day 7 or at 1 month (P0.05). The ALP levels continuously decreased at 3, 6 and 12 months (P0.01). In conclusion, tPTX+AT significantly improves the quality of life and serum biomarker levels of these patients. The convenient surgical removal of the hyperplastic parathyroid gland for postoperative recurrence supports tPTX+AT as the recommended treatment for relevant patients.

Total thyroidectomy is the most common surgical procedure for the treatment of thyroid diseases. Postoperative hypocalcemia/hypoparathyroidism is the most frequent complication after total thyroidectomy. The aim of this study was to evaluate the rate of postoperative hypocalcemia and permanent hypoparathyroidism after total thyroidectomy in order to identify potential risk factors and to evaluate the impact of parathyroid autotransplantation. We performed a retrospective analysis of 1018 patients who underwent total thyroidectomy at our institution between 2000 and 2016. Medical records were reviewed to analyze patient features, clinical presentation, management and postoperative complications. Descriptive and inferential statistics were employed based on the natural scaling of each included variable. Statistical significance was set at p ≤ 0.05. Mean ± SD age was 46.79 ± 15.9 years; 112 (11.7%) were males and 844 (88.3%) females. A total of 642 (67.2%) patients underwent surgery for malignant disease. The rate of postoperative hypocalcemia, transient, protracted and permanent hypoparathyroidism was 32.8%, 14.43%, 18.4% and 3.9%, respectively. Permanent hypoparathyroidism was significantly associated with the number of parathyroid glands remaining in situ (4 glands: 2.5%, 3 glands: 3.8%, 1–2 glands: 13.3%; p ˂ 0.0001) [OR for 1–2 glands in situ = 5.32, CI 95% 2.61–10.82]. Other risk factors related to permanent hypoparathyroidism were obesity (OR 3.56, CI 95% 1.79–7.07), concomitant level VI lymph node dissection (OR 3.04, CI 95% 1.46–6.37) and incidental parathyroidectomy without autotransplantation (OR 3.6, CI 95% 1.85–7.02). Identification and in situ preservation of at least three parathyroid glands were associated with a lower rate of postoperative hypocalcemia (30.4%) and permanent postoperative hypoparathyroidism (2.79%).

To describe CT features of parathyroid carcinomas (PCs) by comparison with benign parathyroid lesions (BPs). This retrospective study comprised 82 patients with 76 BPs (62 adenomas and 14 hyperplastic lesions) and 6 PCs. CT features (size, short-to-long axis ratio, shape, peritumoral infiltration, homogeneity, calcification, attenuation values on unenhanced CT, and contrast enhancement during arterial and venous phases) were compared between PCs and BPs. The diagnostic performance of CT features for diagnosing PCs was calculated for these individual parameters. Short-to-long axis ratio was significantly larger in PCs (0.7 ± 0.1) than in BPs (0.5 ± 0.1, p = 0.004). Irregular shape (33%), the presence of peritumoral infiltration (50%), and calcification (33%) were significantly more common in PCs than BPs. The contrast enhancement value was significantly lower in PCs than BPs during arterial (p = 0.004) and venous phases (p = 0.044). The 100% sensitivity criterion for the short-to-long axis ratio (≥ 0.53), enhancement during arterial phase (≤ 56.6HU), and venous phase (≤ 59.5HU) yielded accuracies (62.1%, 71.9%, and 75.4%, respectively). Irregular shape, peritumoral infiltration, and calcification showed high specificity (98.7%) and accuracy (93.9%, 95.1%, and 93.9%, respectively). CT features of high short-to-long axis ratio, irregular shape, the presence of peritumoral infiltration and calcification, and low contrast enhancement may aid in distinguishing PCs from BPs.

A positive and concordant result of at least two diagnostic modalities is generally recommended prior to focused parathyroidectomy. The aim of this study was to analyze the results of surgery and the accurateness of preoperative ultrasonography (US) as single localization modality in patients who underwent parathyroidectomy without the adjunct of intraoperative Parathormone (PTH) measurement. The cases with a preoperative US as the only localization technique, who underwent parathyroidectomy between 10/1999 and 12/2017, were selected from a prospectively maintained database. Therefore, a total number of 242 patients with a mean age of 58.6 ± 13.7 years were included in the present study. US was performed by referral endocrinologist or by the surgeon during office visits. The overall “cure rate” was 99.2% (240 out of 242 patients). In 228/242 patients (94.2%), a drop of perioperative PTH levels consistent with the definition of cure was observed on the day of surgery. In four of the remaining 14 patients, healing was confirmed by PTH level dropping into the normal range on the first postoperative day. Eight patients were cured after a reoperation was performed at our department. Postoperative complications included one case of permanent recurrent laryngeal nerve palsy (0.4%). If performed by an experienced endocrinologist and/or endocrine surgeon, a positive US could be the only preoperative localization study in patients with pHPT. Moreover, the add-value of intraoperative PTH is limited. Major advantages of US are a very high accuracy, the ease of performance (accessibility) and its cost-effectiveness compared with Sesta-MIBI scintigraphy.

Indocyanine green fluorescence angiography (ICGA) is a new adjunct that has been used in surgical procedures to assess blood flow. This study evaluated the utility of ICGA compared to visual inspection to predict parathyroid function, guide autotransplantation and potentially decrease permanent hypoparathyroidism. This was a retrospective study of patients who underwent total or near-total thyroidectomy (T-NT) between January 2015 and March 2018. Patients with preoperative hyperparathyroidism and those undergoing reoperation were excluded. Patients who had ICGA were compared to T-NT patients without ICGA. Data were analyzed to assess the frequency of autotransplantation and incidence of hypoparathyroidism between groups. In total, 210 patients underwent T-NT: 86 with ICGA and 124 without. Autotransplantation was more common in the ICGA group at 36% compared to 12% in the control (p = 0.0001). There was no correlation with at least one normal parathyroid gland on ICGA and postoperative PTH levels (p = 0.75). There was a difference in having normal postoperative PTH when there were at least two normal parathyroid glands (n = 50) compared to patients with less than two normal ICGA glands (n = 36, p = 0.044). Visual assessment and ICGA assessment of vascularity were in agreement, 245/281 (87%). There were 19 glands (6.8%) that would have undergone autotransplant based on visual inspection that had adequate blood supply on ICGA. Transient hypoparathyroidism was present in 45 out of 124 controls (36%) and 32 out of 86 (37%) in the ICG group. ICGA is a novel technique that may improve the assessment of parathyroid gland blood supply compared to visual inspection. ICGA can guide more appropriate autotransplantation without compromising postoperative parathyroid function. At least two vascularized glands on ICGA may predict postoperative parathyroid gland function.

Saving the parathyroid gland during robotic thyroidectomy is challenging. This study evaluated the application of a novel method, subcapsular saline injection (SCASI), to save the parathyroid gland during bilateral axillo-breast approach (BABA) robotic total thyroidectomy. Of the 81 included patients operated on from 2014 to 2016, 31 and 50 underwent BABA robotic total thyroidectomy with and without SCASI, respectively. Serum concentrations of parathyroid hormone (PTH), calcium, and ionized calcium were measured at 1 day and 9 months postoperatively. Transient hypoparathyroidism was defined as PTH

Identifying the parathyroid gland during surgery may be difficult for surgeons. It is critical for them to be able to locate it during thyroidectomy or parathyroidectomy because of the significant function of the parathyroid in the calcium balance. According to recent reports, intrinsic fluorescence of the parathyroid has been found. There is some evidence to suggest that new equipment can detect the fluorescence via imaging technology. In this study, a newly invented intraoperative fluorescence imaging system and indocyanine green (ICG) dye were applied to detect the parathyroid glands and evaluate the vascularization of the parathyroid. From 1 May to 8 August 2018, 26 patients underwent total thyroidectomy in Zhuhai People’s Hospital. These 26 subjects were recruited in our research. All identified parathyroid glands were scored visually from grade 0 to grade 2 according to the vascularity of the parathyroid before ICG angiography was performed. After ICG angiography, the parathyroid glands were scored from 0 to 2 according to the fluorescence intensity (FI). Visual scores were significantly higher than ICG angiography scores. In the 22 patients with at least one parathyroid gland with an ICG score of 2, postoperative parathyroidism (PTH) levels were in the normal range. Of the four patients with no parathyroid gland with an ICG score of 2, two developed transient hypoparathyroidism, with recovery on postoperative day (POD) 7 for the first patient and after 3 months for the second. This study has shown that a fluorescence imaging system applied with indocyanine green is a safe, easy and effective method to protect the parathyroid and predict postoperative parathyroidism. Chinese Clinical Trial Registry no. ChiCTR1800016864.

Ultrasound localisation of parathyroid glands correlates with gland weight. We hypothesise that gland identification is also dependent on anatomical location. Perrier et al. have described a uniform and reliable nomenclature for parathyroid locations. We aimed to correlate surgeon-performed ultrasound (SUS) with intra-operative Perrier classification and gland weight.Review of a prospectively maintained single operator SUS database of 194 patients referred with non-familial primary hyperparathyroidism (PHPT) at a tertiary centre between 2010 and 2015. Patients underwent MIBI localisation as well as on table SUS. Intra-operative pathological gland locations were classified according to the Perrier nomenclature.Mean weight of pathological glands found and missed by SUS was 1.07 ± 0.1 g and 0.48 ± 0.08 g respectively (p = 0.0001, unpaired t test). The weight of glands identified was greater than that of missed glands for each of the Perrier locations (p 0.001, Mann-Whitney). The proportion of pathological glands found at each Perrier location varied significantly (p 0.0001, Chi Square); so we find proportionally more B-, D-, E- and F-type glands and miss more A- and C-type glands. The median weight of glands missed on SUS varied significantly across the Perrier groups (Kruskal-Wallis, p = 0.0034) and suggests that SUS can miss quite large glands ( 0.5 g) in locations B, C and F; whereas missed glands in locations A, D and E were all small ( 0.5 g).Whilst gland identification correlates well with gland weight, anatomical location has a significant impact on failure of localisation irrespective of gland weight. For the surgeon operating on PHPT patients with negative US localisation, particular attention should be paid to locations C, D and A as these are the sites where pathological glands are most often missed on pre-operative US.

Molecular pathogenesis of parathyroid tumors is incompletely understood. Identification of novel molecules and understanding their role in parathyroid tumorigenesis by proteomics approach would be informative with potential clinical implications. Adenomatous (n = 5) and normal (n = 2) parathyroid tissue lysates were analyzed for protein profile by LC–MS/MS method and the proteins were classified using bioinformatics tools such as PANTHER and toppfun functional enrichment tool. Identified proteins were further validated by western blotting and qRT-PCR (n = 20). Comparative proteomics analysis revealed that a total of 206 proteins (74 upregulated and 132 downregulated) were differentially expressed (≥ twofold change) in adenomas. Bioinformatics analysis revealed that 48 proteins were associated with plasma membrane, 49 with macromolecular complex, 39 were cytoplasm, 38 were organelle related, 21 were cell junction and 10 were extracellular proteins. These proteins belonged to a diverse protein family such as enzymes, transcription factors, cell signalling, cell adhesion, cytoskeleton proteins, receptors, and calcium-binding proteins. The major biological processes predicted for the proteins were a cellular, metabolic and developmental process, cellular localization, and biological regulation. The differentially expressed proteins were found to be associated with MAPK, phospholipase C (PLC) and phosphatidylinositol (PI) signalling pathways, and with chromatin organization. Western blot and qRT-PCR analysis of three proteins (DNAJC2, ACO2, and PRDX2) validated the LC–MS/MS findings. This exploratory study demonstrates the feasibility of proteomics approach in finding the dysregulated proteins in benign parathyroid adenomas, and our preliminary results suggest that MAPK, PLC and PI signalling pathways and chromatin organization are involved in parathyroid tumorigenesis.

The GCM2 gene encodes a transcription factor predominantly expressed in parathyroid cells that is known to be critical for development, proliferation and maintenance of the parathyroid cells. A cohort of 127 Spanish patients with a disorder of calcium metabolism were screened for mutations by Next-Generation Sequencing (NGS). A targeted panel for disorders of calcium and phosphorus metabolism was designed to include 65 genes associated with these disorders. We observed two variants of uncertain significance (p.(Ser487Phe) and p.Asn315Asp), one likely pathogenic (p.Val382Met) and one benign variant (p.Ala393_Gln395dup) in the GCM2 gene in the heterozygous state in five families (two index cases had hypocalcemia and hypoparathyroidism, respectively, and three index cases had primary hyperparathyroidism). Our study shows the utility of NGS in unravelling the genetic origin of some disorders of the calcium and phosphorus metabolism, and confirms the GCM2 gene as an important element for the maintenance of calcium homeostasis. Importantly, a novel variant in the GCM2 gene (p.(Ser487Phe)) has been found in a patient with hypocalcemia. This study was supported by three grants from the Department of Health (2017111014, 2018111097 and 2019111052) and one grant from the Department of Education (IT1281-19) of the Basque Government. This work is generated within the Endocrine European Reference Network (Project ID number of Endo-ERN: 739527). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Background Familial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism. Loss-of-function mutations mainly involving Arg15 residue of the adaptor-related protein complex 2, sigma subunit 1 (AP2S1) cause a rarer, more recently recognized form of FHH, FFH type-3. Recently, 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) showed superior sensitivity to conventional imaging in localizing parathyroid adenomas. We report a new FFH type-3 patient who underwent unnecessary parathyroidectomy in association with misleading FCH-PET/CT imaging. Case presentation A 29-year old woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcemia in 2013. Medical history was positive only for chronic constipation and malaise with no personal or family history of hypercalcemia, kidney stones, or neck surgery. Over seven years, serum calcium level was 2.51–2.89 mmol/L with concomitant PTH level of 58.7–94.8 mmol/L. Serum phosphate levels were in the low/low normal range. Serum creatinine and magnesium levels were normal. 25-hydroxy vitamin D level was 13 nmol/L. 24-hour urine calcium level was 1.92 mmol/day but increased to 6.99 mmol/day after treatment with cholecalciferol 1000 IU daily. Bone mineral density and renal ultrasound were normal. Parathyroid ultrasound showed two hypoechoic nodules inferior to the left and right thyroid lobes; however, 99mtechnitium-sestamibi scans (2013, 2016, 2018) were negative. FCH-PET/CT (2019) showed focal uptake co-localizing with the nodule inferior to the left thyroid lobe. The patient underwent left inferior parathyroidectomy and pathology was consistent with parathyroid hyperplasia. However, postoperatively, serum calcium and PTH levels remained elevated and FCH-PET/CT and ultrasound showed persistence of the uptake/nodule. Whole exome sequencing showed Arg15Cys mutation in the AP2S1 gene characteristic of FHH type-3. Conclusions In this new case of FHH type-3, FCH-PET/CT failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node. This, together with increased urinary calcium after vitamin D supplementation, led to unnecessary parathyroidectomy. Given the increasingly lower cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild PTH-dependent hypercalcemia.

Parathyroid adenoma within or adjacent to the vagus nerve is a rare ectopia, with only 21 cases reported in the literature [1,2,3]. A plausible explanation described by Gilmour in 1937 is that parathyroid elements, destined for the inferior parathyroid glands, may segregate and attach to the nerve during embryogenesis [4, 5].

Background Secondary hyperparathyroidism (SHPT) is a common high-risk factor for mortality in end-stage renal disease, and parathyromatosis and supernumerary parathyroid glands are very rare causes of persistent SHPT. Preoperative diagnosis and removal of all hyperplastic parathyroid glands are challenging. We report a rare case of persistent SHPT due to parathyromatosis and supernumerary parathyroid glands and successful management by multiple imaging modalities. Case presentation A 53-year-old Chinese woman on haemodialysis experienced discomfort due to itching and bone pain due to persistent SHPT after parathyroidectomy. The supernumerary parathyroid glands and parathyromatosis were detected by multiple imaging modalities, including 99mTc-sestamibi (99mTc-MIBI) scans, ultrasonography and four-dimensional computed tomography (4D-CT) and then excised; pathological confirmation was performed. During follow-up, her serum calcium and parathyroid hormone levels were stable in the appropriate ranges, and no complications arose. Conclusions Because of persistent SHPH after parathyroidectomy in patients with haemodialysis, multiple imaging modalities, including 99mTc-MIBI scans, 4D-CT and ultrasonography, are helpful for detecting supernumerary parathyroid glands and parathyromatoses. Accurate preoperative localization of this rare lesion is important for management, enabling the removal of all affected parathyroid tissues.

Background The purpose of present study is to assess the effects of active localization and vascular preservation of inferior parathyroid glands in central neck dissection (CND) for papillary thyroid carcinoma (PTC). Methods A classification of IPGs according to their location and vascular features was developed, and, based on this classification, a CND procedure was designed, and IPGs and their vascular were actively localized and strategically preserved. A total of 197 patients with PTC who underwent a total thyroidectomy and concomitant CND were enrolled. Eighty-nine patients with traditional meticulous fascia dissection were allocated to group A, and 108 patients with active location and vascular preservation of IPGs were allocated to group B. Those with inferior parathyroid glands auto-transplantation in each group were assigned as group At (18) and group Bt (12). Variables including serum intact parathyroid hormone (PTH), total calcium, the incidence of transient, and permanent hypoparathyroidism were studied. Results Compared with group A, serum intact PTH (P < 0.001) and total calcium levels (P < 0.05) in group B significantly improved on the first postoperative day, and the incidence of transient hypoparathyroidism significantly dropped in group B (P < 0.001). A total of 170 patients in the two groups had complete follow-up data. The incidence of permanent hypoparathyroidism significantly decreased in group B, from 8.8% to 1.0% (P = 0.017). However, there were no significant differences in all variables between group Bt and group At. Conclusion Active location and vascular preservation of inferior parathyroid glands effectively protected the function of IPGs in CND for PTC.

Possible ectopic parathyroid hormone (PTH) production in adipose tissues surrounding hyperplastic parathyroid glands was examined in patients with secondary hyperparathyroidism (SHPT). In vitro culture of adipose tissues from 31 patients excised during parathyroidectomy showed PTH secretion in 23 (74.2%) patients. In vitro PTH secretion was detected in adipose tissues adhered to the parathyroid glands from 22 (71.0%) patients, in not-adhered adipose from 11 (35.5%) and in the thymus from four (28.6%) patients. Immunohistochemistry revealed colonies of PTH- and GCM2-positive cells intricately intertwined with adipocytes in excised adipose tissues prior to culture. When pieces of parathyroid parenchyma from SHPT patients were transplanted into the thyroid of immunodeficient nude rats with induced SHPT, the transplants secreted human PTH for one to three-and-half months after transplantation and expressed adipocyte markers, PPARγ2 and perilipin A, that the transplants did not express prior to transplantation. These findings indicate the importance of thoroughly removing adipose tissues surrounding the parathyroid glands when performing parathyroidectomy. We speculate that these ectopic PTH-producing cells are parathyroid parenchymal cells pushed out from the glands along with adipocyte progenitors during nodular growth of hyperplastic parenchymal cells and that these cells proliferate in SHPT, forming colonies PTH-producing cells intricately intertwined with adipocytes.

Background Patients with primary hyperparathyroidism (PHPT) may be asymptomatic, and some may present with normocalcemic PHPT (NPHPT). Patients with vitamin D deficiency may also be asymptomatic, with normal calcium and elevated PTH concentrations. These latter patients are usually diagnosed with vitamin D deficiency-induced secondary hyperparathyroidism (VD-SHPT). Therefore, it is very difficult to distinguish PHPT and NPHPT from VD-SHPT based on calcium or PTH concentrations in clinical settings. In this case-control study, we aimed to verify the diagnostic power of a new parathyroid function index (PFindex = Ca*PTH/P). Methods This study enrolled 128 patients with surgically and pathologically confirmed PHPT, including 36 with NPHPT, at a hospital in West China between January 2009 and September 2017. Thirty-seven patients with VD-SHPT and 45 healthy controls were selected from the population of a cross-sectional epidemiological study as the SHPT and healthy groups, respectively. We used the PFindex to describe the characteristics of PHPT, NPHPT, and VD-SHPT.. Differences between the four groups were compared, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of PFindex. Results The PHPT group had the highest PFindex (454 ± 430), compared to the other three groups (NPHPT: 101 ± 111; SHPT: 21.7 ± 6.38; healthy: 12.2 ± 2.98, all p 34 to differentiate NPHPT from VD-SHPT yielded the highest positive likelihood ratio and lowest negative likelihood ratio. Conclusion The PFindex provided excellent diagnostic power for the differentiation of NPHPT from VD-SHPT. This simple tool may be useful for guiding timely decision-making processes regarding the initiation of vitamin D treatment or surgery for PHPT.

Background In this study, we aimed to compare the kinetics of intact parathyroid hormone (iPTH) during the perioperative period of endoscopic thyroidectomy via bilateral areola approach (ETBAA) in the same period, following a traditional open thyroidectomy approach (OTA). Methods We conducted a prospective observational study of patients who were undergoing thyroidectomy and level VI clearance. Patients who had been affected by papillary thyroid cancer (PTC) were stratified into three groups: those eligible for endoscopic treatment (ETBAA); patients who were eligible for ETBAA but had opted for OTA (OTA-L); and patients who were not suitable for endoscopic intervention (OTA-H). A process for locating parathyroid glands was utilized to stratify gland dissection laboriousness. In Type A, the gland is firmly fixed to thyroid gland. This type can be sub-classified into three subtypes. A1: the parathyroid gland is attached to the inherent thyroid capsule. A2: the gland is partially embedded in the thyroid gland. A3: the gland is located in the thyroid tissue. Type B is defined as a gland which is separated from the thyroid gland. The iPTH was sampled at wound closure. Results There were 100 patients in each group. We found a significant difference between the ETBAA and OTA-H groups for type A2, as well as a loss of parathyroid glands and a number of parathyroid transplantation procedures. The endoscopic group was treated during an earlier stage of thyroid cancer. The iPTH profile of each group decreased, although this was the most consistent in the OTA-H group. A comparison of ETBAA with OTA-L demonstrates that the iPTH level change is similar. Conclusion There is no advantage of endoscopic treatment for preserving parathyroid function.

Surgery for primary hyperparathyroidism is undertaken by many specialties but predominantly endocrine and ear, nose and throat (ENT) surgeons. There is currently no consensus on the peri-operative management of primary hyperparathyroidism. We sought to determine current surgical practice and identify any inter-specialty variation in the United Kingdom (UK). An online survey was disseminated to members of the British Association of Endocrine & Thyroid Surgeons (BAETS) in the UK. 78 surgeons responded (40 Endocrine, 37 ENT and 1 maxillofacial). 90% of surgeons used ultrasound and sestamibi for pre-operative localisation. Intraoperative frozen section (31%) and parathyroid hormone monitoring (41%) were the most common adjuncts used intraoperatively. 68% of surgeons did not use any wound drains. Nearly two-thirds of surgeons (64%) discharged patients from the clinic within 3 months, There were some significant differences (p

Background Parathyroid carcinoma is a rare malignancy with an increasing incidence. Most patients are characterized by the presence of severe primary hyperparathyroidism, especially hypercalcemia, while patients with normal level of serum calcium are extremely rare. Unfortunately, patients free of hypercalcemia are usually diagnosed at a later stage and suffer from a rather poor prognosis. Case presentation We describe a patient diagnosed with intrathyroidal normocalcemic parathyroid carcinoma, whose preoperative ultrasonography suggests that the tumor is located inside the thyroid gland and present without obvious clinical manifestations, which makes it more challenging for diagnosis. Conclusions Preoperative suspicion of malignancy is of great importance for advanced management while preoperative diagnosis is rather challenging with the limited contribution of imaging examinations. Any abnormality in serum level of calcium or parathormone may help to make an initial diagnosis especially when the level is extremely high. We introduce this case of initial misdiagnosis of an intrathyroidal parathyroid carcinoma, mimicking a suspicious thyroid nodule, to focus on the possible anomalous presentations of this rare condition and on its optimal management.

BackgroundSecondary hyperparathyroidism is a common complication in patients with chronic kidney disease that requires vigilant treatment due to its high mortality rate. Pharmacologic therapy is recommended as an initial treatment; if there is no response, a total parathyroidectomy is performed. In some cases, surgery is accompanied by auto-transplantation of parathyroid tissue.Case presentationThe patient was diagnosed with chronic kidney disease and received a kidney transplant. However, due to rejection of the transplanted kidney, medical nephrectomy was carried out and routine hemodialysis was initiated and observed. At this time, secondary hyperparathyroidism with elevated parathyroid hormone and hyperphosphatemia developed and pharmacologic treatment was applied. However, there was no response to pharmacologic treatment; therefore, total parathyroidectomy with auto-transplantation was performed. Eight years after surgery, a growing mass was observed in the transplantation site, accompanied by an elevation of parathyroid hormone. A complete resection of the mass was performed, and the patient was diagnosed with parathyroid carcinoma. Additional adjuvant radiation therapy was ordered, and the patient is being monitored.ConclusionsThis is a rare but remarkable case of parathyroid carcinoma arising from auto-transplanted parathyroid tissue after total parathyroidectomy in a patient with secondary hyperparathyroidism. We suggest caution should be taken when choosing to auto- transplant parathyroid tissue and that careful postoperative observation should be performed.